Compositions for topical treatment

ABSTRACT

A stable, self-preserving, antimicrobial, composition suitable for the treatment of a variety of dermal as well as subcutaneous conditions. The compositions include as an active ingredient a quaternary ammonium compound, preferably benzethonium chloride, potentiated and synergized with menthyl lactate cooling agent in a cationic carrier. Optionally, a phenoxyethanol preservative and chlorhexidine digluconate antibacterial agent may be used to assist in enhancing the activity. The compositions kill a broad spectrum of gram-negative and gram-positive bacteria, fungus and yeasts. The compositions are used as first aid skin treatments and as skin sanitizers to help prevent bacterial contamination of minor cuts, scrapes and burns. The compositions are particularly useful when applied to the skin after hair removal in that they additionally cool, soothe and moisturize the skin. The compositions may also serve as a base vehicle in which additional skin care ingredients may be added to provide additional functionality to the compositions.

BACKGROUND OF THE INVENTION

This invention relates generally to compositions for applying to theskin, and more particularly to an improved multi-purpose topicallyapplied, self-preserving, antimicrobial, composition suitable for thetreatment of a variety of dermal as well as subcutaneous conditions. Thecompositions may optionally be combined with other medicaments, whereinit serves as a vehicle for topical application. The compositions possessbroad-spectrum rapid kill properties and are useful as skin sanitizers.The compositions are particularly useful for preventing microbialcontamination of the skin after hair removal.

While many dermal conditions are the result of internal body chemistry,and require the services of a medical provider, many relatively simpleskin conditions may often be treated at by using non-prescription (OTC)type remedies. Typical of such conditions are teenage acne, itching,swelling, as well as rashes caused by bacterial and microbialconditions. Individual remedies are known in the art for treating suchconditions.

Some common pathogens that often cause skin infections includeStaphylococcus aureus (methicillin sensitive and resistant variants);Pseudomonas aeruginosa; and E. coli. Common pathogenic forms of fungiand yeasts include Trichophyton, Tinea and Candida albicans. One of themajor concerns of product manufacturers and end users of beauty productssuch as salons is the risk of microbial contamination and outbreaks ofinfections. In order to minimize this risk, the industry uses variousstrategies including preservatives, single use products andcleaning/sanitization procedures. The compositions of this invention areparticularly useful in decreasing the risk of microbial contamination tothe client in such spas or treatment facilities.

NUFREE® Finipil® (Equibal Labs, Unionville, N.Y.; U.S. Pat. No.7,078,050 to Fusco) is a known mild bacteriostat and fungicide that istypically used after hair removal for slowing down hair regrowth and forsoothing the skin.

Possibly relevant US patents and US patent application Publications thatApplicant is aware of at the time of filing this application are thefollowing:

US 2002/0034524 to Poret US 2003/0049212 to Robinson et al. US2004/0022822 to Poret. US 2004/0161435 to Gupta US 2005/0025737 A1 toSebagh US 2005/0084471 to Andrews et al US 2005/0053595 to FuscoUS2005/0249763 to Lesendre et al. US 2006/0115440 A1 to Arata et al. US2009/0186943 to Ikeda et al. US 2009/0197948 to Miyahara et al. US2009/0203649 to Kato et al. US 2009/0214628 to de Rijk US 2009/0226498to Flugge-Berendes et al. US 2010/0196504 to Schmaus et al US2010/0216889 to Modak et al US 2011/0070316 to Modak et al. US2012/0148516 to Abel et al. US 2012/0201902 to Modak et al. US2012/0276219 to Taylor et al. US 2013/0005807 to Ishida et al U.S. Pat.No. 5,879,684 to Fox U.S. Pat. No. 5,997,893 to Jampani et al U.S. Pat.No. 6,022,551 to Jampani et al U.S. Pat. No. 6,022,565 to Albert et alU.S. Pat. No. 6,528,070 to Bratescu et al U.S. Pat. No. 7,078,050 toFusco U.S. Pat. No. 7,842,726 to Aoki et al. U.S. Pat. No. 7,871,649 toModak et al. U.S. Pat. No. 8,173,143 to Tecco et al. U.S. Pat. No.8,198,326 to Scholz U.S. Pat. No. 8,293,802 to Modak et al U.S. Pat. No.8,337,872 to Fuls et al.

Possibly relevant non-patent literature that Applicant is aware of atthe time of filing this application are listed in the InformationDisclosure Statement submitted with this application and copies aresubmitted therewith.

The entire disclosures of all of these aforementioned patents,publications and literature are incorporated herein by reference.

SUMMARY OF THE INVENTION

The invention is directed to topical, stable, self-preserving,antimicrobial, composition suitable for the treatment of a variety ofdermal as well as subcutaneous conditions that includes an activeingredient a quaternary ammonium compound, preferably benzethoniumchloride, potentiated and synergized with menthyl lactate in a cationiccarrier. Optionally, a phenoxyethanol preservative and chlorhexidinedigluconate antibacterial agent may be used to assist in enhancing theactivity. The compositions kill a broad spectrum of gram-negative andgram-positive bacteria, fungus and yeasts. The compositions are used asfirst aid skin treatments and as skin sanitizers to help preventbacterial contamination of minor cuts, scrapes and burns. Thecompositions are particularly useful when applied to the skin after hairremoval in that they additionally cool, soothe and moisturize the skin.The compositions may also serve as a base vehicle in which additionalskin care ingredients may be added to provide additional functionalityto the compositions.

DETAILED DESCRIPTION OF THE DISCLOSED EMBODIMENT

Broadly, the present invention is directed to stable antibacterial andantimicrobial composition that includes a combination of anantimicrobial quaternary ammonium compound with menthyl lactate coolingagent in a cationic carrier containing at least one other skin carecomponent.

Generally, the composition includes the following ingredients and rangesof ingredients:

Water 40.0-90.0% Thickening agent: 0.1-1.0% Cationic synthetic ornatural polymers Anti-microbial agent: 0.01-0.2%  quaternary ammoniumcompounds Saturated fatty acids 0.1-1.0% Cationic conditioners 0.1-10.0% Cationic emulsifiers  1.0-10.0% Emollients 0.1-10%  Fattyalcohols 0.1-3.0% Cooling agents  1.0-10.0% Herbal Extracts 0.1-5.0%Anti-irritants 0.1-1.0% Preservatives 0.01-1.0% 

All ingredients are in weight/weight percent (w/w %), i.e., the weightof the ingredient relative to the weight of the final compositiondescribed as a percentage.

Water

The stable antibacterial and antimicrobial compositions of thisinvention contain from 40% to 90% water. In the preferred composition,the water is deionized water at a concentration of about 85%.

Thickening Agent: Cationic Synthetic or Natural Polymers

The composition of this invention additionally includes cationicthickening agents. The cationic thickening agents that may be used inthis invention include Polyquaternium 10, 11, 16, 24, 37, and 67,chitosan and guar hydroxypropyltrimonium chloride, hydroxyethylcetyldimonium phosphate, guar hydroxypropyltrimonium Chloride.

The preferred cationic thickening agent is Ultragel 300 (CognisCorporation), also known as polyquaternium-37, and is a quaterniumammonium polymer consisting of primarily Ethanaminium,N,N,N-trimethyl-2-((2-methyl-1-oxo-2-propenyl)oxy)-, chloride,homopolymer. This composition is a cationic polymeric thickenertypically used for producing transparent gel products in an acidic pH.

Preferred concentrations are from 0.1 to 1.0% by weight, with a highlyconcentration of 0.7% by weight.

Anti-Microbial Agent: Quaternary Ammonium Compounds

The preferred quaternary ammonium antimicrobial agent is benzethoniumchloride. Benzethonium chloride is a monoalkyltrimethyl ammonium salt.This compound is an odorless white solid; soluble in water. It hassurfactant, antiseptic, and anti-infective properties, and it is used asa topical antimicrobial agent in first aid antiseptics. It is also foundin cosmetics and toiletries such as mouthwashes, anti-itch ointments,and antibacterial moist towelettes. Benzethonium chloride is also usedin the food industry as a hard surface disinfectant.

Benzethonium chloride exhibits a broad spectrum of microbiocidalactivity against bacteria, fungi, mold and viruses. Independent testingshows that benzethonium chloride is highly effective against suchpathogens as methicillin-resistant Staphylococcus aureus, Salmonella,Escherichia coli, Clostridium difficile, hepatitis B virus, hepatitis Cvirus, herpes simplex virus (HSV), human immunodeficiency virus (HIV),respiratory syncytial virus (RSV), and norovirus.

The US Food and Drug Administration (FDA) specify that the safe andeffective concentrations for benzethonium chloride are 0.1-0.2% in firstaid and healthcare antiseptic drug products. Aqueous solutions ofbenzethonium chloride are not absorbed through the skin. It is notapproved in the US and Europe for use as a food additive.

In addition to its highly effective antimicrobial activity, benzethoniumchloride contains a positively charged nitrogen atom covalently bondedto four carbon atoms. This positive charge attracts it to the skin andhair. This contributes to a soft, powdery after feel on the skin andhair, as well as long-lasting persistent activity againstmicroorganisms.

Benzethonium chloride is available under trade names Lonzagard,Salanine, BZT, Diapp, Quatrachlor, Polymine D, Phemithyn, Antiseptol,Disilyn, Phermerol, and others.

Other quaternary ammonium antimicrobial compounds that may be used aloneor in combination with other similar compounds are methylbenzethoniumchloride and benzalkonium chloride. If these antibacterial agents areused, the preferred concentrations are 0.01 to 0.13% by weight forbenzalkonium chloride and 0.01 to 0.5% by weight methylbenzethoniumchloride.

Other antibacterial agents that may be used, either alone or incombination are PCMX (para chloro neta xylenol), triclosan, ethanol,iodine and iodine complexes (e.g. PVI)

Saturated Fatty Acids

Saturated fatty acids selected from the group consisting of caprylicacid, capric acid, lauric acid, myristic acid, palmitic acid, stearicacid, arachidic acid, behenic acid, lignoceric acid, and cerotic acid.The preferred compositions of this invention include stearic acid, asaturated fatty acid with an 18 carbon chain and has the IUPAC nameoctadecanoic acid. The preferred concentration is from about 0.1 to 1.0%by weight, with a highly preferred concentration of 0.4% by weight.

Cationic Conditioners

Cationic conditioners and emulsifiers, which may be used according tothe invention, include behentrimonium methosulfate, cetrimoniumchloride, myristamidopropyl PG-dimonium chloride phosphate, brassicylisoleucinate esylate.

The preferred composition of this invention includes behentrimmiummethosulfate, with quantities of cetyl alcohol and butylene glycol,i.e., Incroquat™ Behenyl TMS-50 (Croda International, Plc). It assistsin forming cationic skin care emulsions that impart wash resistantmoisturizing benefits and a soft, smooth skin feel. Broadly, theconcentration is from about 0.1 to 10.0% by weight, with a preferredconcentration of 1.0% to 10% by weight, with a highly preferredcomposition at about 4% by weight.

Other cationic conditioners that can be used are Incroquat behenyl TMS,Incroquat behenyl TMS 50, cetrimonium chloride, distearyldimoniumchloride, and stearalkonium chloride.

Emollients

Emollients selected from the group consisting of silicone fluids,emollient esters, emollient ethers, natural (avocado, coconut,safflower, etc.) and synthetic oils (mineral). The preferredcompositions of this invention include dimethicones, preferably linear,polydimethylsiloxanes with viscosities ranging from 1.5 cSt to 20million cSt. They are clear, colorless, odorless and inert fluids andare characterized by their softening effect on skin and hair. They arehydrophobic without restricting respiration of the skin that makes thembeneficial in skin creams and lotions. Broadly, the concentration isfrom about 0.1 to 10.0% by weight, with a highly preferred compositionat about 0.15% by weight.

Fatty Alcohols

Preferred fatty alcohols are selected from the group consisting oftert-Butyl alcohol, tert-Amyl alcohol, 3-Methyl-3-pentanol,ethchlorvynol, capryl alcohol, 2-ethyl hexanol, pelargonic alcohol,capric alcohol, undecyl alcohol, lauryl alcohol, tridecyl alcohol,myristyl alcohol, pentadecyl alcohol, cetyl alcohol, palmitoleylalcohol, heptadecyl alcohol, stearyl alcohol, nonadecyl alcohol,arachidyl alcohol, heneicosyl alcohol, behenyl alcohol, erucyl alcohol,lignoceryl alcohol, ceryl alcohol, 1-heptacosanol, montanyl alcohol,cluytyl alcohol, myricyl alcohol, melissyl alcohol, geddyl alcohol, andcetearyl alcohol, oleyl Alcohol and octyldodecanol.

The preferred compositions of this invention include 2-octyldodecanol,Eutanol® G (Cognis). This is a “medium spreading” emollient that ishydrolysis stable and typically used in formulations where a wide pHrange is needed e.g. deodorants, antiperspirants, cosmetic andpharmaceutical skin care preparations and for hair remover formulations.

The preferred compositions of this invention also include cetyl alcohol,also known as 1-hexadecanol and palmityl alcohol, is a fatty alcoholwith the formula CH3(CH2)150H.

Broadly, the concentration of fatty alcohol is from about 0.1 to 3.0% byweight, with a preferred composition containing 0.1 to 3.0% by weight2-octyldodecanol and 0.1% to 2.0% phenoxyethanol, with the highlypreferred composition containing 3.0% by weight 2-octyldodecanol and0.5% phenoxyethanol.

Cooling Agents

The compositions of this invention further include a cooling agent,which provides, when applied to the skin, a cooling or soothing feeling.The highly preferred cooling agent used in this invention is menthyllactate. Other cooling agents, which may be used according to theinvention, include, but are not limited to natural and synthetic mentholderivatives. Menthyl lactate (Frescolate®) has a mild, cooling, fresh,minty, somewhat burnt sugar like and sweet menthol taste profile. It isused in minty compounds for various purposes such as toothpaste, chewinggum and tobacco. It is also used in confections, beverages, and as apeppermint booster in oral care products. Menthyl lactate is produced intwo forms, a white crystalline powder and fused material; both forms areused in various applications. It has been discovered that in a cationiccarrier the antimicrobial agent is potentiated and synergized withmenthyl lactate cooling agent. Broadly, the concentration is from about1.0 to 10.0% by weight, with a highly preferred composition at about4.5% by weight.

Herbal Extracts and Anti-Irritants

Herbal extracts and anti-irritants selected from the group consisting ofchamomile, bisabolol, aloe vera, panthenol, zinc salts, calendula, oatextracts, azulene, camellia oil, witch-hazel extract. The preferredcompositions of this invention also include chamomile or chamomile. Thisis a common name for several daisy-like plants of the family Asteraceae.

It is preferred to add chamomile to skin cosmetics to serve as anemollient and its anti-inflammatory effects. Broadly, the concentrationis from about 0.1 to 5.0% by weight, with a highly preferred compositionat about 0.3% by weight.

The preferred compositions of this invention also contain witch hazel asan astringent. Broadly, the concentration is from about 0.1 to 5.0% byweight, with a highly preferred composition at about 0.3% by weight.

The preferred composition of this invention also include bisabolol, ormore formally a+) bisabolol or levomenol. This is a natural monocyclicsesquiterpene alcohol. It is colorless, viscous oil that is the primaryconstituent of the essential oil from German chamomile (Matricariarecutita) and Myoporum crassifolium. It is almost insoluble in water andglycerin, but soluble in ethanol. Bisabolol has a weak sweet floralaroma and is used in various fragrances. Bisabolol is known to haveanti-irritant, anti-inflammatory and anti-microbial properties.Bisabolol is also demonstrated to enhance the percutaneous absorption ofcertain molecules. Broadly, the concentration is from about 0.1 to 1.0%by weight, with a highly preferred composition at about 0.3% by weight.

Humectants selected from the groups consisting of glycerin, propyleneglycol, polyethylene glycol, glycereth-26, acetamide MEA, sorbitol mayalso be added to the composition.

Preservatives

The topical compositions of this invention also contain a preservativeor preservative system to inhibit the growth of pathogens over anextended period. The preferred preservative system consists of one ormore of the following ingredients, chlorhexidine and its salts,polyhexamethylene biguanide, alexidine, triclosan,parachlorometaxylenol, zinc pyrithione, silver and silver salts,parabens, Methylisothiazolinone, organic acids (citric, acetic, sorbic,lactate), phenoxyethanol, phenethyethanol, essential oils (tea tree,eucaplyptus, thyme). The preferred preservative is Neolone 100, which isphenoxyethanaol available from Dow. Other suitable preservatives for usemay be used, although Neolone 100 is the preferred.

The preferred compositions of this invention also include chlorhexidinedigluconate, i.e., CHG (20%). This is a 20% aqueous solution of 1,6-BIS(N—P-Chlorophenyl-Biguanido) and Hexane Digluconate and has powerfulactivity against bacteria and fungi at low concentrations. It iseffective against gram-negative and gram-positive bacteria. Itseffectiveness is enhanced in alcohols and its activity is unaffected bythe presence of blood and other biological fluids. Broadly, theconcentration of preservative is from about 0.01 to 1.0% by weight, witha highly preferred composition at about 0.25% by weight.

Other preservatives that can be used alone or in combination herein areChlorhexidine gluconate, chlorhexidine acetate, chlorhexidine chloride,and chlorhexidine, free-base, Phenoxyethanol, parabens, such as methylparaben, ethyl parabens, propyl parabens, butyl paraben and synergisticparaben blends, Kathon, acidifiers, such as citric, acetic, latic, malicacids, silver and silver salts, copper and copper salts, zinc and zincsalts, DMDM Hydantoin, Imidazolidinyl Urea, lodopropynyl ButylCarbamate, Benzoic Acid, Sodium benzoate, Potassium benzoate, PHMB, Zincpyrithione.

Additional Ingredients

The topical, stable, self-preserving, antimicrobial, compositions ofthis invention may further include other ingredients to provide adesired functionality, for example:

Sunscreens

aminobenzoic acid, arobenzone, cinoxate, diioxybenzone, homosalate,menthyl anthranilate, octocrylene, octyl methoxycinnamate, octylsalicylate, oxybenzoate, padimate 0, phenylbenzimidazole, sulfonic acid,sulisobenzone, titanium dioxide, trolamine salicylate and zinc oxide.

Antimicrobials

The compositions of the invention may further include one or moreadditional antimicrobial agents, for example antiviral, antibacterial,or antifungal substances. Antimicrobial agents also include substancespossessing any combination of virucidal or virustatic, bacteriocidal orbacteriostatic, or fungicidal or fungistatic properties.

Examples of antimicrobial agents include, but are not limited to,iodophors, iodine, benzoic acid, dehydro acetic acid, propionic acid,sorbic acid, methyl paraben, ethyl paraben, propyl paraben, butylparaben, cetrimide, chlorhexidine (free base and/or salts), otherbiguanides, such as polyhexamethylene biguanide (PHMB) andpolyaminopropyl biguanide (PAPB), chloroeresol, chloroxylenol, benzylalcohol, bronopol, chlorbutanol, ethanol, isopropyl alcohol, n-propanol,phenoxyethanol, phenylethyl alcohol, 2,4-dichlorobenzyl alcohol,thiomersal, clindamycin, erythromycin, benzoyl peroxide, mupirocin,bacitracin, polymyxin B, neomycin, triclosan, parachlorometaxylenol,foscarnet, miconazole, fluconazole, itriconazole, ketoconazole, andpharmaceutically acceptable salts thereof.

Antibiotics

The compositions of the invention may further include one or moreantibiotics such as penicillin (natural, semi-synthetic and synthetic),minocycline, rifampin, fluoroquinolones (ciprofloxacin), nalidixic acid,sulfa drugs (sulfadiazine, sulfamethoxazole, sulfacetamide,sulfadoxine), silver (metallic and nano) and silver salts (silversulfadiazine, silver nitrate, silver oxide, silver carbonate, silverchloride), copper and copper salts, zinc and zinc salts, ethyl alcohol,mupirocin, and benzoyl peroxide.

Wax Emulsifiers

The compositions of the invention may further include one or more solidwaxy esters, for example, Myristyl Myristate, Cetyl Palmitate, MyristylStearate, Stearyl Behenate, Behenyl Isostearate, Isostearyl Behenate,Behenyl Behenate, Lauryl Behenate, Behenyl Erucate, Polawax, forexample, cationic: Incroquat TMS, Incroquat TMS50 (Croda International,Plc)

The following is a list of ingredients in the preferred compositions ofthis invention and the ranges of such ingredients that may be used.

% Range (w/w) (about % INGREDIENT Generic name Preferred w/w) Deionizedwater Water 84.8 40.0-90.0 Ultragel 300 or Quaternary 0.7 0.1-1.0*Polyquarternium-37 ammonium polymer Benzethonium 0.2 .01-0.2 ChlorideEmersol 13 Stearic Acid 0.4 0.1-1.0 (Stearic acid) Eutanol G2-octyldodecanol 3.0 0.1-3.0 Incroquat Behentrimonium 4.0  1.0-10.0Behenyl TMS-50 methosulfate (and) Cetyl alcohol (and) Butylene glycolDimethicone DC200 Linear 0.15 0.1-10  Polydimethylsiloxane Fluids Cetylalcohol 1-hexadecanol 0.6  .5-3.0 or palmityl alcohol Frescolate MenthylLactate 4.5 1.0 10.0 Neolone PH 100 Phenoxyethanol 0.5 0.1-2.0 Chamomileextract Matricaria 0.3 0.1-5.0 Chamomile Recutita Extract Witch hazelextract Hamamelis Virginiana 0.3 0.1-5.0 Bisabolol α-(−)-bisabolol oralso 0.3 0.1-1.0 known as levomenol CHG (20%) 20% Chlorhexidine 0.25.001-.5  Gluconate Solution *Polyquaternium-37, i.e.,Poly(2-methacryloxyethyltrimethylammonium chloride)

The highly preferred stable, antimicrobial topical treatment compositionconsists essentially of the following ingredients and concentrations(weight percent):

Water 84.8% Quaternary ammonium polymer 0.7% Benzethonium Chloride 0.2%Stearic Acid 0.4% 2-octyldodecanol 3.0% Behentrimonium methosulfate 4.0%Linear Polydimethylsiloxane fluids 0.15% Cetyl alcohol .6% MenthylLactate 4.5% Phenoxyethanol 0.5% Chamomile Extract 0.3% Witch hazelextract 0.3% Bisabalol 0.3% 20% Chlorhexidine Gluconate .25% Solution

The combination of ingredients in the composition of this invention,when properly combined, form a unique antibacterial and antimicrobialcomposition. The composition can be used as a first aid skin treatmentto help prevent bacterial contamination of minor cuts, scrapes andburns. The composition cools, soothes and moisturizes the skin afterhair removal. The composition kills bacteria, fungus and yeast,including Staphlocococus aureus, Pseudomonas aeruginosa, Escherichiacoli, Aspergillus brasiliensis, and Candida albicans.

The composition, although useful as a topical application after hairremoval, may also be used as an anti-inflammatory for poison ivy, acneand other type skin disorders, a sanitizer and as an antiseptic firstaid composition.

The compositions, although preferably liquid, made be made into a spray,cream gel and lotion for different applications.

The ingredients for the compositions of this invention, particularly thepreferred compositions, are chemically compatible with each other.Broadly, the process of the producing the compositions, includes thefollowing:

Step A. Combine the selected amounts of water, cationic synthetic ornatural polymers until fully blended at 16 C.°-25 C.°. Continue blendingand heat to a range of 55 C.° to 75 C.° and hold for a period of time.

Step B. Heat to 40 C.° to 75 C.° and blend the selected amounts ofCationic conditioners, Cationic emulsifiers, Fatty alcohols, SaturatedFatty Acids, Cooling agents and emollients and hold for a period oftime.

Step C. Add the selected amount Antimicrobial Quaternary Ammoniumcompounds and blend with the mixture of Step A at 60 C.° to 70 C.°

Step D. Combine and Blend mixture of Step C with that of Step A andbegin cooling the blend to 22 C.° to 35 C.°.

Step E. During the cooling step of Step D when the temperature reaches40 C.° to 35 C.°. blend in the Herbal Extracts, Anti Irritants,Preservatives. Continue Blending until the desired Viscosity isachieved.

The following are some specific, non-limiting examples of thecompositions of this invention. The compositions may further includeadditional ingredients, which do not substantially affect theantimicrobial activities of the composition.

Example 1 First Aid Antiseptic and Soothing Lotion Comprising

Deionized water (USP) 81.4% w/w  DC200 Dimethicone 1.0% w/w DehyquartC4046 4.0% w/w Benzethonium chloride 0.2% w/w Cyclomethicone 5.0% w/wFrescolat ML 4.5% w/w Chlorhexidine gluconate (20%) 0.2% w/w Eutanol G3.0% w/w Phenoxyethanol 0.7% w/w

Observations:

The composition remains stable after three freeze/thaw cycles, i.e., theingredients are compatible and the composition is stable.

Example 2 First Aid Antiseptic Lotion

Deionized water (USP) 83.0% w/w  DC200 Dimethicone 1.0% w/w Incroquatbehenyl TMS 50 4.0% w/w Benzethonium chloride 0.2% w/w Witch hazelextract 0.3% w/w Frescolat ML 4.5% w/w Chlorhexidine gluconate (20%)1.0% w/w Eutanol G 3.0% w/w Phenoxyethanol 0.7% w/w Cyclomethicone 5.0%w/w Bisabolol 0.3% w/w

Observations:

The formulation is very liquid and does not survive the freeze/thaw testdue to separation. This indicates some incompatibility between one ormore ingredients.

Example 3 First Aid Antiseptic and Cooling Cream

Deionized water (USP) 78.7% w/w  DC200 Dimethicone 1.0% w/w Crodafos CES6.0% w/w Benzethonium chloride 0.2% w/w Witch hazel extract 0.3% w/wFrescolat ML 4.5% w/w Chlorhexidine gluconate (20%) 1.0% w/w Zemea 3.0%w/w Phenoxyethanol 0.7% w/w Cyclomethicone 5.0% w/w Bisabolol 0.3% w/w

Observations:

The formulation is stable after 3 freeze/thaw cycles

Example 4 First Aid Antiseptic and Skin Sanitizing Cooling Cream

Deionized water (USP) 84.6% w/w  DC200 Dimethicone 1.0% w/w Eutanol G3.0% w/w Chamomile extract 0.3% w/w Benzethonium chloride 0.2% w/w Witchhazel extract 0.3% w/w Frescolat ML 4.5% w/w Chlorhexidine gluconate(20%) 1.0% w/w Stearic acid 0.4% w/w Cetyl alcohol 0.6% w/w Ultragel 3000.7% w/w Phenoxyethanol 0.7% w/w Incroquat TMS50 4.0% w/w Bisabolol 0.3%w/w

Observations:

The formulation is stable after 3 freeze/thaw cycles.

Antimicrobial Activity

This example determines the antimicrobial activity of the preferredcomposition of this invention (hereinafter “OTC”) as an OTC antisepticcream using a modified time kill method based on ASTM E2315-03 and azone of inhibition assay.

-   -   1. Equibal Labs Finipil® Batch#04092612 (the composition of U.S.        Pat. No. 7,078,050 to Fusco, “Finipil”)    -   2. The preferred composition of this invention with 0.2%        Benzethonium chloride; Batch #01021913 (“OTC”)—Example 4, above.        -   a. Note: All the following OTC compositions are Example 4            herein.

The following tests are used to determine the efficacy of the OTCformulation compared to the original Finipil formulation and acompetitive product:

Example A Modified ASTM Method E2315-03 In Vitro 10 Minute Time KillAssays

An aliquot of 0.8 ml of test product (Finipil® is tested against S.aureus) is pre-warmed to 35° C. is mixed with 0.2 ml of a mixture of 50%culture (approx 22 hours old), diluted to 0.45 OD at 600 nm with theappropriate medium and sterile bovine adult serum (so that the BAScomprises 50% of the inoculum's volume) and mixed well. The tubes arethen incubated at 35° C. for 10 minutes. After the time has elapsed, 0.2ml of the contents of the tube is transferred to a tube containing 4.8ml of D/E broth to quench the antimicrobial activity. After thoroughlymixing the contents to ensure that the product is evenly suspended, 0.5ml of is plated on TSA (SDA plates for yeast and fungus) plates areincubated for 24-48 hours at 35° C. to 37° C. (up to five days at 21° C.for fungus).

As a control, 0.8 ml of sterile normal saline is substituted for thetest product. 0.5 ml of the control sample is plated after processing asfollows: the control is diluted according to the same initial dilutionscheme as the test samples followed by a dilution in TSB of 1:1000 for afinal dilution of 1:50,000 (0.01 ml of the 1:50 dilution tube: 9.99 mlTSB) and 0.5 ml of this final dilution are plated on TSA. In the case ofyeast, the control samples are diluted 1:100 with SDB for a finaldilution of 1:5000 plated on SDA. The fungus control is diluted andplated in the same manner as the test samples using SDA.

A saline+DIE broth uninoculated blank is also subcultured to ensuresterility of the media and technique.

Test Organisms:

a. Staphylococcus aureus ATCC #6538b. Pseudomonas aeruginosa ATCC #9027c. Escherichia coli ATCC #8739d. Staphylococcus aureus ATCC #33592 (Methicillin Resistant)e. Aspergillus brasiliensis ATCC #16404f. Candida albicans ATCC #10231

Test Groups:

-   -   3. Equibal Labs Finipil®; Batch#04092612 (the composition of        U.S. Pat. No. 7,078,050 to Fusco, “Finipil”)    -   4. “OTC” as described in Formula 4 above    -   5. Competitive cream-commercially available post delapitory        cream

Results:

TABLE 1 Results expressed as % reduction of microbes in the test groupversus the control group after a 10 minute exposure. OTC CompetitiveProduct Challenge Control % reduc- % reduc- Organism cfu/ml cfu/ml tioncfu/ml tion S. aureus 4.4 × 10⁷ <49 >99.9998 3.4 × 10⁷ 22.73 ATCC 6538S. aureus 3.1 × 10⁷ <49 >99.9998 2.3 × 10⁷ 27.42 ATCC 33592 P.aeruginosa 2.9 × 10⁸ <49 >99.9999 1.6 × 10⁸ 44.83 ATCC 9027 E. coli 1.9× 10⁸ <49 >99.9999 1.4 × 10⁸ 29 ATCC 8739 C. albicans 1.2 × 10⁶<49 >99.996 1.1 × 10⁶ 8.33 ATCC 10231 A. brasiliensis 2.5 × 10³ <49 >981.6 × 10³ 38 ATCC 16404 OTC (0.2% BZT) Finipil Challenge Control %reduc- % reduc- Organism cfu/ml cfu/ml tion cfu/ml tion S. aureus 3.7 ×10⁷ <49 >99.9999 2.4 × 10⁷ 36.49 ATCC 6538

The OTC formulation is highly efficacious compared to either thecompetitive product or the Finipil. Only the OTC group meets the FDArequirements of a 3 log reduction of pathogens in 10 minutes.

Example B Zone of Inhibition Test Comparing OTC and One CompetitiveProduct

An overnight culture of the test organism is diluted to 0.40 OD at 600nm and then further diluted 10⁻² to obtain approximately 3×10⁶ CFU/mlfor the inoculation of TSA or SDA plates as follows: a 0.5 ml volume isspread across the surface of a sterile agar plate and allowed to dry. A7 mm well is made in the center of the agar plate and approximately 0.2ml of product is pipetted into the well. Additionally, Finipil is testedagainst S. aureus. The plates are incubated at 37° C. for 24 hours andthe zones of inhibition are determined by measuring the diameter of theclear circular area around the product filled well.

The following organisms will be used for this test:

Staphylococcus aureus ATCC 6538 (MSSA)*Staphylococcus aureus ATCC 33592 (MRSA)*Pseudomonas aeruginosa ATCC 9027Escherichia coli ATCC 8739Candida albicans ATCC 10231Aspergillus brasiliensis ATCC #16404*Becton Dickinson BBL Cefoxitin 30 microgram Sensi-Disk® sensitivitydisks will be used to indicate susceptibility to Methicillin

Results:

TABLE 2 Zone of inhibition test comparing OTC, Finipil and onecompetitive product. Cefoxitin Competitive Challenge disk OTC ProductFinipil Organism Zone (mm) Zone (mm) Zone (mm) Zone (mm) S. aureus 33 2411 12 ATCC 6538 S. aureus 10 24 13 ND ATCC 33592* P. aeruginosa ND 15 10ND ATCC 9027 E. coli ND 17 8 ND ATCC 8739 C. albicans ND 13 0 ND ATCC10231 A. brasiliensis ND 15 14 ND ATCC 16404 ND = Not done;*Characterized as Methicillin resistant by ATCC

OTC shows broad-spectrum activity against all of the pathogens tested.The competitive product and the Finipil® showed low level inhibition ofgrowth. The competitive product does not appear to possess any activity,even over a 24 hour time period against C. albicans ATCC 10231.

The activity of OTC does not appear to be affected by the resistanceprofile of the S. aureus variant used as the challenge organism. As thedata in the above table shows, S. aureus ATCC 33592 shows significantresistance to Cefoxitin, a Methicillin analog, compared to a knownMethicillin-sensitive isolate, S. aureus ATCC 6538, where the Cefoxitinsensitivity disk produced a large zone of inhibition.

Example C Modified ASTM Method E2315-03 In Vitro 15 Second Time KillAssays Comparing a) Finipil with 0.2% w/w Benzethonium Chloride Added,b) Finipil, and c) OTC

The purpose of this test is to compare the antibacterial efficacy of a)Finipil with 0.2% w/w benzethonium chloride added, b) Finipil, and c)OTC.

A 0.9 ml volume of test product is mixed with 0.1 ml of an overnightculture (approx 22 hours old) of S. aureus ATCC 6538, diluted to 0.45 ODat 600 nm, and mixed for 15 seconds. After the time has elapsed, 0.2 mlof the culture/product is removed and added to 4.8 ml of D/E brothquench antimicrobial the activity and a 0.5 ml aliquot is plated on TSA.The TSA plates are incubated for 24-48 hours at 35° C. to 37° C. As acontrol, 0.9 ml of sterile normal saline is substituted for the testproducts. 0.5 ml of the control is plated after a 1:1000 dilution of theD/E broth tube (0.01 ml: 9.99 ml). A saline+D/E broth uninoculated blankis also subcultured to ensure sterility of the media and technique.

Results:

TABLE 3 Comparative kill rate of OTC and Finipil with and withoutbenzethonium chloride (BZT) % Reduction in 15 seconds Challenge OrganismOTC Finipil Finipil + BZT S. aureus ATCC 6538 99.95 20 32

OTC exhibits superior antibacterial activity against S. aureus ATCC 6538compared to the original Finipil formula or the original Finipil formulawith the mere addition of 0.2% BZT. The addition of benzethoniumchloride to the Finipil formula does not seem to provide any significantboost to the antibacterial effect. Without being bound to any particulartheory, this may be due to the binding or complexing of the cationic BZTwith anionic or non-ionic ingredients. The cationic nature of the OTCappears to enhance the activity of the BZT and may also support thesynergistic antibacterial effect of one or more of the ingredients. Itis also notable that the menthyl lactate does not appear to have anysignificant antibacterial efficacy (20% reduction) in a non-cationicbased formulation such as Finipil.

Example D Modified ASTM Method E2315-03 In Vitro 15 Second Time KillAssays for the Determination of the Efficacy of OTC as a Health CareAntiseptic Drug Product

The same test protocol is used as described in Example C above.

Results:

% Reduction in 15 seconds Challenge Organism OTC P. aeruginosa ATCC9027 >99.99996 S. aureus ATCC 6538 99.99 S. aureus ATCC 33592* 99.9 E.coli ATCC 8739 99.99999 C. albicans ATCC 10231 99.998

OTC meets the efficacy requirements of the FDA TFM for healthcareantiseptic drug products against the pathogens tested.

Example E

Determination of the combined and separate antibacterial effects ofbenzethonium chloride and menthyl lactate in the cationic base used inthe OTC formulation.

Briefly, OTC and derivative formulations are made as follows:

1) OTC with 4.5% w/w menthyl lactate without benzethonium chloride

2) OTC with 0.2% benzethonium chloride without menthyl lactate

3) OTC with both 0.2% benzethonium chloride and 4.5% menthyl lactate

The formulations are tested using the same test protocol is used asdescribed in Example C above.

Results:

15 second log₁₀ reduction in CFU from control OTC OTC without ChallengeOrganism OTC without BZT menthyl lactate S. aureus ATCC 6538 4.0 1.2 2.6

The results indicate the following: 1) that there is a slight synergybetween the BZT and menthyl lactate, and 2) the antimicrobial activityof menthyl lactate is greater in a cationic base compared to an anionicbase. Without being bound to any particular theory, this same phenomenonmay hold true for other natural, semi-synthetic, and fully syntheticmenthol derivatives.

In summary, the compositions of this invention may be used as a firstaid skin treatment to help prevent bacterial contamination of minorcuts, scrapes and burns. Unexpectedly the antimicrobial efficacy isvastly greater in a cationic system. There appears to be a potentiationor synergism between the quaternary ammonium compounds and the menthyllactate in a cationicsystem.

It is preferred to use the compositions immediately after the removal ofhair from the skin, weather by shaving, waxing, depilatory cream shavesor the use of wax free, non-aqueous (anhydrous) liquid depilatories,e.g., NUFREE® brand depilatories (Equibal Labs, Unionville, N.Y.). Seealso U.S. Ser. No. 13/712,937 filed on Dec. 12, 2012 entitledAntibacterial Hair Removal Composition to Normajean Fusco. The entiredisclosure of this application is incorporated herein by reference. Thecompositions cool, soothe and moisturize the skin after hair removal.

More specifically, the compositions of this invention are 100% effectiveas an antibacterial, antimicrobial treatment. The compositions killbacteria, fungus and yeast, including Staphlococccus aureus, MRSA,Pseudomonas aeruginosa, Escherichia coli, Aspergillus brasiliensis, andCandida albicans.

When applied to the skin after shaving or hair removal it cools,shrinks, reduces swelling and protects the empty hair follicles,increases elasticity in the hair follicle wall, breaks fats and oils toprevent clogging of the hair follicle, atrophies new hair growth, andwhen used daily, drops the temperature of the empty follicle, freezingaway swelling due to water retention, hot showers or aerobic workoutsand protects against in-grown hairs and rids the area of old in-growns.

The compositions of this invention may also be used when you need anantibacterial and antimicrobial skin treatment along with instantcooling and soothing. It may also be used during a manicure or pedicureto heal and soothe cuticle damage, and kills fungus or used on feet atthe health club to reduce swelling and prevent the growth of bacteria.The composition may also be used to sooth chapped lips and cold sores.Due to the rapid kill capabilities demonstrated by the compositions ofthis invention, they may be used as a healthcare antiseptics and handsanitizers.

1. A stable, antimicrobial composition comprising: a. a cationic basecomposition containing an amount of a cationic thickener, an amount of acationic emulsifier, and an amount of cationic conditioning agent; b. aneffective antimicrobial amount of at least one cationic antimicrobialagent; and c. an amount of a menthol-based cooling agent.
 2. Theantimicrobial composition of claim 1, wherein the amount cooling agentin the antimicrobial composition is between 0.1 to 7.0% by weight. 3.The antimicrobial composition of claim 1, wherein the effectiveantimicrobial amount of the cationic antimicrobial agent is between0.01% to 5% by weight.
 4. The antimicrobial composition of claim 1wherein the cationic antimicrobial agent is selected from the groupconsisting of biguanides, quaternary ammonium compounds and peptides. 5.The antimicrobial composition of claim 4, wherein: a. the biguanide isselected from the group consisting of chlorhexidine free base and itssalts, polyhexamethylene biguanide (PHMB), polyaminopropyl biguanide(PAPB) and alexidine, b. the quaternary ammonium compound is selectedfrom the group consisting of benzalkonium chloride, benzethoniumchloride, methylbenzethonium chloride, cetrimonium chloride, c. thepeptide is lysine.
 6. The antimicrobial composition of claim 1, whereinthe cationic antimicrobial agent is selected from the group consistingof: a. Benzethonium chloride wherein the effective antimicrobial amountis from 0.01 to 0.2% w/w b. Benzalkonium chloride wherein the effectiveantimicrobial amount is from 0.01 to 0.13% w/w c. Methylbenzethoniumchloride wherein the effective antimicrobial amount is 0.01 to 0.5% w/wd. Para chloro meta xylenol (PCMX) e. Triclosan f. Ethanol, and g.iodine and iodine complexes (e.g. PVI)
 7. The antimicrobial compositionof claim 1, wherein the cationic thickener is selected from the group ofacrylic homopolymers (PQ-37), quaternized celluloses (PQ-10), cationicguar gum, and chitosan.
 8. The antimicrobial composition of claim 1,further comprising an amount of a non-ionic thickener.
 9. Theantimicrobial composition of claim 1, further comprising an amount of anon-ionic emulsifying agent and an amount of a non-ionic conditioningagent.
 10. A stable, antimicrobial composition comprising: Water40.0-90.0% Thickening agent: 0.1-1.0% Cationic synthetic or naturalpolymer Anti-microbial agent: 0.01-0.2% quaternary ammonium compoundSaturated fatty acid 0.1-1.0% Cationic conditioner 0.1-10.0% Cationicemulsifier 0.1-10.0% Emollient 0.1-10% Fatty alcohol 0.1-3.0% Coolingagent 1.0-10.0% Herbal Extract 0.1-5.0% Anti-irritant 0.1-1.0%Preservative 0.01-1.0%


11. A stable, antimicrobial composition comprising, by weight percent:Water 40.0-90.0% Quaternary ammonium polymer 0.1-1.0% BenzethoniumChloride .01-0.2% Stearic Acid 0.1-1.0% 2-octyldodecanol 0.1-3.0%Behentrimonium methosulfate 1.0-10.0% Linear Polydimethylsiloxane fluids0.1-10% Cetyl alcohol .5-3.0% Menthyl Lactate 1.0-10.0% Phenoxyethanol0.1-2.0% Chamomile Extract 0.1-5.0% Witch hazel extract 0.1-5.0%Bisabalol 0.1-1.0% 20% Chlorhexidine Gluconate .001-1.0% Solution


12. A stable, antimicrobial composition comprising, by weight percent:Water 84.8% Quaternary ammonium polymer 0.7% Benzethonium Chloride 0.2%Stearic Acid 0.4% 2-octyldodecanol 3.0% Behentrimonium methosulfate 4.0%Linear Polydimethylsiloxane fluids 0.15% Cetyl alcohol .6% MenthylLactate 4.5% Phenoxyethanol 0.5% Chamomile Extract 0.3% Witch hazelextract 0.3% Bisabalol 0.3% 20% Chlorhexidine Gluconate 0.25% Solution


13. A method of preventing bacterial contamination to skin comprisingapplying to the skin an effective amount of the composition of claim 1.14. A method of preventing bacterial contamination to skin comprisingapplying to the skin an effective amount of the composition of claim 10.15. A method of preventing bacterial contamination to skin comprisingapplying to the skin in an effective amount of the composition of claim11.
 16. A method of preventing bacterial contamination to skincomprising applying to the skin an effective amount of the compositionof claim
 12. 17. A method of preventing bacterial contamination to skinhaving minor cuts scrapes or burns comprising applying to the skin aneffective amount of the composition of claim
 1. 18. A method ofpreventing bacterial contamination to skin having minor cuts scrapes orburns comprising applying to the skin an effective amount of thecomposition of claim
 10. 19. A method of preventing bacterialcontamination to skin having minor cuts scrapes or burns comprisingapplying to the skin an effective amount of the composition of claim 11.20. A method of preventing bacterial contamination to skin having minorcuts scrapes or burns comprising applying to the skin an effectiveamount of the composition of claim
 12. 21. A method of preventingbacterial contamination to skin after hair removal comprising applyingto the skin an effective amount of the composition of claim
 1. 22. Amethod of preventing bacterial contamination to skin after hair removalcomprising applying to the skin an effective amount of the compositionof claim
 10. 23. A method of preventing bacterial contamination to skinafter hair removal comprising applying to the skin an effective amountof the composition of claim
 11. 24. A method of preventing bacterialcontamination to skin after hair removal comprising applying to the skinan effective amount of the composition of claim 12.